title: Design of benzothiazole-1,3,4-thiadiazole conjugates: synthesis and anticonvulsant evaluation.
abstract: Various 2-[(6-substituted-1,3-benzothiazol-2-yl)amino]-N-[5-substituted-phenyl-1,3,4-thiadiazol-2-yl]acetamides were synthesized with a prospective exploration of "lead hopping", using pharmacophoric elements for in vivo anticonvulsant activity. This yielded three potent candidates (5i, 5t, and 5u) in the preliminary screening employing the maximal electroshock seizure (MES) and the subcutaneous pentylenetetrazole (scPTZ) test, showing minimal neurotoxicity. Their quantitative study indicated an increase of nearly 2-10 times for the MES test and 7- to 67-fold for the scPTZ test in the protective index, the keystone in drug discovery for anticonvulsant activity.
authors.affiliation: Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Jamia Hamdard, Hamdard Nagar, New Delhi, India.
authors.forename: Nadeem
authors.initials: N
authors.lastname: Siddiqui
authors.forename: Priya
authors.initials: P
authors.lastname: Ahuja
authors.forename: Sachin
authors.initials: S
authors.lastname: Malik
authors.forename: Satish K
authors.initials: SK
authors.lastname: Arya
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D052160:Benzothiazoles / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D015195:Drug Design; D004597:Electroshock; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D015394:Molecular Structure; D010433:Pentylenetetrazole; D017208:Rats, Wistar; D012640:Seizures / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D013329:Structure-Activity Relationship; D013830:Thiadiazoles / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D000927:Anticonvulsants; D052160:Benzothiazoles; D013830:Thiadiazoles; C058949:1,3,4-thiadiazole; D005680:gamma-Aminobutyric Acid; C005465:benzothiazole; D010433:Pentylenetetrazole
keywords: Anticonvulsants; Benzothiazole; Neurotoxicity; Phenytoin; Thiadiazole